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  • Title: Predictors of thrombohemorrhagic early death in children and adolescents with t(15;17)-positive acute promyelocytic leukemia treated with ATRA and chemotherapy.
    Author: Abla O, Ribeiro RC, Testi AM, Montesinos P, Creutzig U, Sung L, Di Giuseppe G, Stephens D, Feusner JH, Powell BL, Hasle H, Kaspers GJL, Dalla-Pozza L, Lassaletta A, Tallman MS, Locatelli F, Reinhardt D, Lo-Coco F, Hitzler J, Sanz MA.
    Journal: Ann Hematol; 2017 Sep; 96(9):1449-1456. PubMed ID: 28597167.
    Abstract:
    Clinical trials on childhood acute promyelocytic leukemia (APL) report early death (ED) rates of 3-8%, but predictors of thrombohemorrhagic (TH)-ED are not well understood. In a retrospective study, we aimed to determine the incidence and predictors of TH-ED in childhood APL. Data were analyzed from children and adolescents with t(15;17)-positive APL (n = 683) who started treatment with all-trans retinoic acid (ATRA) and chemotherapy in different international studies. Demographic data; initial white blood cell (WBC), peripheral blood (PB) blast, and platelet counts; hemoglobin value; coagulation parameters; morphologic variant (M3 or M3v); and induction details were analyzed. Early death was defined as death occurring within 30 days of presentation. The incidence of ED was 4.7% (32 of 683 patients). Predictors of TH-ED were identified by univariable and multivariable Cox proportional hazard regression analyses (n = 25). In univariable analysis, high WBC (>10 × 109/L) (P < 0.001) and high PB blast (>30 × 109/L) (P < 0.001), M3v (P < 0.01), and black ethnicity (P < 0.001) were independent predictors of TH-ED. In multivariable analysis, high WBC count (P < 0.01) and obesity (i.e., body mass index ≥95th percentile for age) (P = 0.03) were predictors of TH-ED. Initial high WBC counts and obesity are likely predictors of TH-ED in childhood APL. The efficacy of novel drugs for APL-associated coagulopathy or of frontline arsenic trioxide and ATRA combination regimens in reducing ED rates in childhood APL remains to be established.
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